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PubMed1997

[Plasmosorption in combined therapy of psoriasis].

Combined therapy with plasmosorption has been performed in 22 patients aged 18-65 years suffering from different variants of psoriasis diagnosed 5 to 24 years before. Stable remission was achieved in 16 patients who exhibited normalization of peripheral blood characteristics including total protein and protein plasma fractions, lowering of CIC and middle molecular peptides concentration. The response was also obtained in severe psoriasis (psoriatic erythrodermia and arthropathic psoriasis). 11 patients remained in remission for at least 1 year. Due to plasmosorption the hospital stay of the patients reduced. Plasmosorption promoted detoxication, recovery of hepatic protein-synthetizing function, enhancement of plasma albumin detoxication ability.

Adolescent↗
PubMed2005

Combination therapy in the management of hypertension: focus on angiotensin receptor blockers combined with diuretics.

There is increasing evidence that combination therapy should be emphasized more than it is at present for the initial treatment of hypertensive patients. Recent guidelines acknowledge the value of combination therapy, although some treatment algorithms fail to echo this message. Observations from major clinical trials in the elderly, diabetics, stroke patients, and African Americans all indicate that combination therapy is necessary to control blood pressure in the majority of these patients. Several combination therapies such as an angiotensin II receptor blocker and a diuretic, an angiotensin-converting enzyme inhibitor with a diuretic, a beta blocker with a diuretic, or an angiotensin-converting enzyme inhibitor with a calcium antagonist have been shown to be effective in patients who do not respond to monotherapy. The current review focuses on the newest such combination; an angiotensin II receptor blocker and a diuretic may have an added advantage of being well tolerated. Recent studies have shown that angiotensin II receptor blockers, given alone or combined with a diuretic, may prevent some cardiovascular outcomes independent of their blood pressure-lowering efficacy.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2005

Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes.

Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms (each 2 months) and 2 washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy when compared with simvastatin or ramipril alone (P<0.001 by ANOVA). When compared with simvastatin or ramipril alone, combined therapy significantly reduced high-sensitivity C-reactive protein levels (P=0.004 by ANOVA). Interestingly, combined therapy or ramipril alone significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone (P<0.015 by ANOVA). Ramipril combined with simvastatin had beneficial vascular and metabolic effects when compared with monotherapy in patients with type 2 diabetes.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

Triple antiviral therapy in HCV positive patients who failed prior combination therapy.

AIM: To assess the efficacy of triple therapy (peginte-rferon or high dose standard interferon, plus ribavirin and amantadine) in nonresponders to prior combination therapy. METHODS: A total of 196 patients were enrolled in a multicenter, open, randomized study. Patients were given 180 mug/wk of peginterferon-alpha-2a (40 kDa) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d) for 48 wk (group A) or interferon-alpha-2a (6 MU/d for 4 wk, 3 MU/d for 20 wk, and 3 MU tiw for 24 wk) plus ribavirin (800-1000 mg/d) and amantadine (200 mg/d) for 48 wk (group B). RESULTS: Overall sustained virologic response (SVR) was 26.6% (32.1% and 19.5% in group A and B, P = 0.057). Baseline ALT > 120 UI/L (OR 2.4; 95% CI: 1.11 to 5.20; P = 0.026) and HCV RNA negativity after 12 wk (OR 8.7; 95% CI: 3.87 to 19.74; P < 0.0001) were independently associated with SVR. Therapy discontinuation occurred less frequently in patients treated with peginterferon than standard interferon (P = 0.036). CONCLUSION: More than 25% of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy, especially if they have a high baseline ALT and are treated with pegylated interferon.

Adolescent↗
PubMed2005

Controlled-release nifedipine and candesartan low-dose combination therapy in patients with essential hypertension: the NICE Combi (Nifedipine and Candesartan Combination) Study.

OBJECTIVE: To compare the clinical efficacy of low-dose controlled-release (CR) nifedipine (20 mg/day) plus candesartan (8 mg/day) combination therapy with that of up-titrated candesartan (12 mg/day) monotherapy. DESIGN: Randomized, double-blind study. SETTING: Outpatient study. PATIENTS AND PARTICIPANTS: Patients with essential hypertension, who did not achieve their target blood pressure with baseline treatment of candesartan 8 mg/day for 8 weeks. MAIN OUTCOME MEASURES: Blood pressure, pulse pressure, urinary microalbumin excretion. RESULTS: Blood pressure was significantly reduced in both groups (P < 0.05), but the reduction was significantly greater in the combination therapy group (12.1 +/- 1.4/8.7 +/- 0.9 mmHg) than in the up-titrated monotherapy group (4.1 +/- 1.4/4.6 +/- 0.9 mmHg) (P < 0.0001). The reduction in pulse pressure was significantly greater in the combination therapy group (3.3 +/- 1.2 mmHg) than in the up-titrated monotherapy group (0.7 +/- 1.2 mmHg) (P = 0.0031). Urinary microalbumin excretion decreased significantly in the combination therapy group (from 61.9 to 40.5 mg/g creatinine; P < 0.05), but not in the up-titrated monotherapy group. CONCLUSIONS: These findings suggest that the low-dose combination therapy of nifedipine CR and candesartan is superior to the up-titrated monotherapy of candesartan in terms of blood pressure control and renal protection in patients with essential hypertension.

Adolescent↗
PubMed1991

Preliminary results of clinical application of reactor fast neutrons in radiation and combined therapy of patients with laryngeal carcinoma.

Since 1985 treatment of cancer patients on BR-10 reactor has been carried out in the Institute of Medical Radiology. Till May, 1989, 78 patients have received mixed gamma-neutron therapy and combined treatment (preoperative radiation therapy and surgery). Marked late local reactions (perichondritis) were observed only in three (7%) out of 42 patients treated with radical radiation therapy alone. 43 patients had a follow-up period of two years. Among them T2 tumors were registered in six (14%) cases, T3 in 28 (65%) cases, T4 in nine (21%) cases. Regional metastases were observed in 13 (30%) patients. 19 out of 27 patients (70%) treated with radical gamma-neutron therapy and 13 out of 16 patients (81%) treated with combined therapy using reactor fast neutrons as preoperative radiation therapy are alive two years without evidence of the disease.

Adult↗
PubMed1990

Treatment-resistant alopecia areata. Response to combination therapy with minoxidil plus anthralin.

Combination therapy with 5% minoxidil plus 0.5% anthralin was used to treat 51 patients with severe treatment-resistant alopecia areata. History of a cosmetically inadequate response to one or both drugs used as a single agent was present in 50 of the 51 patients. Therapy was relatively well tolerated except by 1 patient who developed a severe irritant reaction and was dropped from the study. Mild to moderate irritant dermatitis was seen in all remaining patients. Cosmetic response was seen in 5 (11%) of 45 patients who completed the 6-month study. Cosmetic response was maintained in 4 (80%) of 5 patients who continued treatment for as long as 84 weeks. All responders had evidence of hair regrowth by week 12. The rapidity and extent of hair regrowth were greater with combination therapy than with either drug used as a single agent. Serum and 24-hour urinary minoxidil determinations showed enhanced systemic minoxidil absorption, which was probably secondary to the irritant dermatitis in some patients; however, no clinical evidence of a systemic minoxidil effect was found. These data suggest that combination therapy using drugs with probable different mechanisms of action may provide a synergistic effect in alopecia areata.

Administration, Topical↗
PubMed2005

Combination therapy for osteoporosis: considerations and controversy.

Combination therapy, the simultaneous use of two pharmaceutical agents with the goal being reduction of fracture risk, is an area of substantial clinical interest. This paper summarizes the rationale, existing clinical trials data, and other considerations relevant to combination therapy for osteoporosis. Combinations of antiresorbers (eg, estrogen plus bisphosphonates) produce greater increases in bone mass than either treatment alone. Conversely, combining anabolic agents (parathyroid hormone) with bisphosphonates does not produce additive effects. None of the existing studies are large enough to determine whether combination treatment reduces fracture risk to a greater extent than use of a single agent. However, it is certain that combination treatment will increase cost and likely that it will increase side effects and reduce therapy adherence. Given the absence of demonstrated fracture reduction benefit, increased cost and likely increase in adverse events, combination therapy is not currently recommended.

Alendronate↗
PubMed2005

Combination therapy for osteoporosis: considerations and controversy.

Combination therapy, the simultaneous use of two pharmaceutical agents with the goal being reduction of fracture risk, is an area of substantial clinical interest. This paper summarizes the rationale, existing clinical trials data, and other considerations relevant to combination therapy for osteoporosis. Combinations of antiresorbers (eg, estrogen plus bisphosphonates) produce greater increases in bone mass than either treatment alone. Conversely, combining anabolic agents (parathyroid hormone) with bisphosphonates does not produce additive effects. None of the existing studies are large enough to determine whether combination treatment reduces fracture risk to a greater extent than use of a single agent. However, it is certain that combination treatment will increase cost and likely that it will increase side effects and reduce therapy adherence. Given the absence of demonstrated fracture reduction benefit, increased cost and likely increase in adverse events, combination therapy is not currently recommended.

Bone Resorption↗
PubMedDate not supplied

Combination therapy with ursodeoxycholic acid and colchicine for primary biliary cirrhosis.

Twelve patients with primary biliary cirrhosis (PBC), stages I to III, received long-term therapy with a combination of 600 mg ursodeoxycholic acid (UDCA) and 1 mg colchicine given daily for more than 2 years. Drug toxicity was mild; one patient experienced diarrhoea that was probably due to colchicine. Serum levels of bilirubin, alkaline phosphatase (ALPase), gamma-glutamyl transpeptidase and alanine aminotransferase decreased by more than 50% of the initial values. Serum albumin and cholesterol levels also improved, but immunoglobulins and anti-mitochondrial antibody titre did not change. Histologic features in the eight patients who received serial liver biopsies before and 2 years after the beginning of treatment were evaluated. Piecemeal necrosis and portal inflammation were improved, but there was no change in portal fibrosis. Patients were divided into two groups; the first received both drugs from the outset, and the second group were started on UDCA for 3 months followed by the addition of colchicine. After 3 months, the improvement in serum bilirubin and ALPase in the first group was greater than in the second. However, in the second group, the ALPase levels had decreased significantly when measured at 6 and 9 months after the treatment compared with the levels at 3 months. These findings suggest that UDCA and colchicine may have a synergistic effect. This combination therapy appears to be safe and effective, both clinically and histologically, for treating PBC.

Colchicine↗
PubMed2001

Unstable angina and non-ST-segment elevation myocardial infarction: perspectives on combination therapy.

We reviewed recent clinical data on the management of unstable angina and non-ST segment elevation myocardial infarction. We concentrated on the use of new therapies, particularly in combination with both older agents and other new methods, in order to present health care providers with an overview of available treatment options. The clinical trials reviewed herein provide strong evidence and proof of principle that combination therapies targeting 1) platelet function (aspirin, thienopyridines, and GP IIb/IIIa antagonists), 2) the coagulation cascade (unfractionated heparin and low-molecular-weight heparin), and 3) the physical characteristics of the active lesion (percutaneous intervention) reduce the risk of death or ischemic complications after thrombotic progression of coronary atherosclerosis.

Adenosine Diphosphate↗
PubMed2005

Fludarabine combination therapy is highly effective in first-line and salvage treatment of patients with Waldenström's macroglobulinemia.

Alkylating agents or single-agent purine analogues are modestly effective as front-line therapy for Waldenstrom's macroglobulinemia (WM), but response rates of < 50% are exhibited in the salvage therapy setting. Fludarabine combination therapy may be more effective, but no large studies exploring these regimens specifically in WM are available. We report our results of 18 cycles of fludarabine combination therapy: FC (fludarabine 25 mg/m2 for 3 days plus cyclophosphamide 250 mg/m2 for 3 days; n = 9), FM (fludarabine 25 mg/m2 for 3 days plus mitoxantrone 10 mg/m2 for 1 day; n = 3), FCR (FC plus rituximab 375 mg/m2; n = 5), or fludarabine/rituximab (n = 1). Four patients had previously untreated disease, and 14 had pretreated disease; 67% had elevated serum levels of beta2-microglobulin, and 86% had hemoglobin levels < or = 12 g/dL. Patients received a median of 4 cycles (range, 1-6 cycles), with grade > or = 3 neutropenia and infection complicating 25% and 4% of cycles, respectively. Objective responses (all partial) were attained in 13 patients (76%). Response rates did not significantly differ by regimen, previous treatment, age, performance status, beta2-microglobulin level, hemoglobin level, time from diagnosis, previous fludarabine exposure, or alkylator refractoriness. Median remission duration was 38 months; no previously untreated patient had died at a median of 37 months of follow-up, and the actuarial 5-year survival rate was 55% for pretreated patients. No cases of secondary myelodysplasia or leukemia were encountered.

Adult↗
PubMed2002

[A clinical evaluation on the combination therapy with ACE-I and ARB, and with ARB and CCB in patients with progressive chronic renal diseases].

Due to therapy resistant hypertension, combination antihypertensive therapy is indispensable for retarding the progression of chronic renal diseases. The majority of pilot studies investigating the renoprotective effect of ACE-I plus ARB revealed a better anti-proteinuric effect of this combination than either of the monotherapies for patients with either diabetic or non-diabetic renal diseases. In contrast, the effect of combination therapy with ACE-I/ARB plus CCB in protecting the kidney from hypertension appeared to be still a matter of controversy. Although the combined therapy with ACE-I plus ARB is superior to that with CCB plus ARB to achieve a greater reduction in urinary protein excretion than either of the monotherapies, one must be aware of the potential hazards associated with the former combined therapy such as worsening of renal anemia and hyperkalemia, especially in patients with impaired renal function. Whether add-on ARB to ACE-I or CCB causes antiproteinuric effects or long-term renoprotection requires larger and longer prospective, randomized controlled trials in the future.

Angiotensin Receptor Antagonists↗
PubMed1993

Empiric monotherapy versus combination therapy of nosocomial pneumonia in trauma patients.

Combination therapy for nosocomial pneumonia with a beta-lactam and aminoglycoside is widely accepted because of synergy and reduction of resistant bacteria. This prospective study of 109 trauma patients (94 blunt, 15 penetrating) with nosocomial pneumonia was performed in consecutive phases. In phase 1, patients were randomized to an anti-pseudomonal third-generation cephalosporin--cefoperazone or ceftazidime. Gentamicin was added to each regimen in phase 2. The mean age of the patients was 37 years, the mean ISS was 31, and there were no differences among the four treatment groups relative to associated injuries. Patients receiving monotherapy had a 56% cure rate compared with 31% for combination therapy (p < 0.04). Persistence rates were similar in these two groups (15% and 20%), but superinfection was significantly higher in the combination group (49% vs. 28%; p < 0.04). The predominant superinfecting organism was methicillin-resistant Staphylococcus aureus (MRSA). Nine patients died (5% monotherapy, 10% combination), and eight had a superinfection. We conclude that monotherapy had a higher cure rate than combination therapy for empiric therapy of pneumonia in our trauma patients. Combination therapy failed because of superinfection (primarily MRSA). Emergence of MRSA may be from host overgrowth or plasmid-mediated induction of resistance, possibly caused by gentamicin.

Adolescent↗
PubMed2001

Low-dose combination therapy: the rationalization for an ACE inhibitor and a calcium channel blocker in higher risk patients.

As more high-risk hypertensives are treated and the need for more intensive antihypertensive therapy is recognized, combination therapies are increasingly used. For initial therapy, particularly for relatively low-risk patients, low-dose combinations are often appropriate. For those who require additional therapy, higher doses of combinations may provide further efficacy while minimizing dose-dependent side effects of monotherapy, thereby improving adherence to therapy. Those combination agents should provide 24-h control with one daily dose, thereby ensuring protection in the early morning hours. Combining an angiotensin converting enzyme inhibitor and a calcium channel blocker is a rational approach to treating hypertension. Not only does it provide significantly better blood pressure control than individual components used as monotherapy, it also minimizes dose-dependent side effects. Also, combining agents from different classes results in complementary mechanisms of action that provide other cardiovascular protective benefits.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2006

The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients.

The proinflammatory mediator CD40 ligand plays an important role in atherogenesis. Biological mechanisms underlying statin and angiotensin II type 1 receptor blocker therapies differ. Therefore, we compared the effects of these therapies either alone or in combination on plasma soluble CD40 ligand (sCD40L). This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-seven hypertensive, hypercholesterolemic patients were given simvastatin 20mg and placebo, simvastatin 20mg and losartan 100mg, or losartan 100mg and placebo daily during each 2 month treatment period. Simvastatin alone did not significantly reduce sCD40L levels relative to baseline measurements when the entire cohort was analyzed. However, simvastatin significantly reduced sCD40L levels from 5.10+/-0.34 to 3.07+/-0.43ng/ml (P=0.002) in a subgroup of 18 patients with high baseline sCD40L levels >2.95ng/ml. Combined therapy or losartan alone significantly decreased plasma sCD40L levels relative to baseline measurements by 14+/-7% (P=0.001) and 13+/-10% (P=0.001), respectively. These decreases were significantly greater than those observed with simvastatin alone (P=0.023 by ANOVA). Significant inverse correlations between baseline sCD40L levels and percent changes in sCD40L levels were observed (r=-0.456, P=0.001 after simvastatin alone; r=-0.476, P<0.001 after combined therapy; r=-0.451, P=0.002 after losartan alone). Losartan alone or combined therapy significantly reduced plasma sCD40L levels more than simvastatin alone in our subjects. Simvastatin, losartan and combined therapy significantly reduced sCD40L to the greatest extent in patients with high baseline sCD40L levels.

Antihypertensive Agents↗
PubMed2003

Mutations in the NS5A and E2-PePHD regions of hepatitis C virus genotype 1b and response to combination therapy of interferon plus ribavirin.

BACKGROUND/AIMS: Combination therapy with interferon (IFN) and ribavirin is the current standard treatment for chronic hepatitis C, but the efficacy is still not satisfactory, especially for genotype 1b. NS5A and E2 proteins of hepatitis C virus (HCV) may repress the IFN-induced RNA-dependent protein kinase (PKR), and thus have the potential to influence the response of HCV to IFN therapy; however, this issue remains controversial. METHODS: Nucleotide sequences of the PKR-eIF2alpha phosphorylation homology domain (E2-PePHD) and PKR-binding domain (NS5A-PKR bd) of the HCV genome were analyzed by amplification and direct sequencing in 30 HCV genotype 1b patients who had been treated with IFN and ribavirin. RESULTS: Nine (30%) patients achieved a sustained virological response (SVR) to combination therapy. Pretreatment variables and amino acid substitutions were compared between responders and non-responders. The responders were younger than non-responders (37.2 +/- 10.4 vs. 45.4 +/- 9.5 years, P = 0.017), whereas no significant statistical differences were found in the number of amino acid substitutions in NS5A and E2-PePHD regions between the two groups. CONCLUSIONS: Genetic heterogeneity in NS5A and E2-PePHD regions of the HCV genome may not serve as a predictor for treatment outcome with combination therapy in Taiwanese patients with chronic HCV genotype 1b infection.

Adult↗